Clinical Trial Results:
A 3-part Open-label Study to Assess the Pharmacokinetics of Lanthanum Carbonate, Compare the Efficacy, Safety and Tolerability of 8 Weeks of Treatment With Lanthanum Carbonate and Calcium Carbonate using a Crossover design and Investigate the Efficacy and Safety of 8 Months of Treatment With Lanthanum Carbonate in Hyperphosphataemic Children and Adolescents Aged 10 years to <18 Years With Chronic Kidney Disease on Dialysis
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Summary
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EudraCT number |
2012-000171-17 |
Trial protocol |
HU DE PL Outside EU/EEA CZ RO |
Global end of trial date |
16 Nov 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
31 May 2019
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First version publication date |
31 May 2019
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
SPD405-207
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01696279 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Shire
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Sponsor organisation address |
300 Shire Way, Lexington, United States, MA 02421
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Public contact |
Study Contact, Shire, 1 866-8425335, ClinicalTransparency@shire.com
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Scientific contact |
Study Contact, Shire, 1 866-8425335, ClinicalTransparency@shire.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000637-PIP01-09 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
16 Nov 2018
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
16 Nov 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of this study was to summarize the percentage of subjects achieving age-specific Kidney Disease Outcomes Quality Initiative (KDOQI) targets for serum phosphorus in hyperphosphatemic children and adolescents with chronic kidney disease (CKD) who were on dialysis, following 8 weeks of treatment with lanthanum carbonate.
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Protection of trial subjects |
This study was conducted in accordance with International Council for Harmonisation of Good Clinical Practice, the principles of the Declaration of Helsinki, as well as other applicable local ethical and legal requirements
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 Feb 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Chile: 5
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Country: Number of subjects enrolled |
Hungary: 20
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Country: Number of subjects enrolled |
Czech Republic: 4
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Country: Number of subjects enrolled |
Poland: 11
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Country: Number of subjects enrolled |
Russian Federation: 15
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Country: Number of subjects enrolled |
Turkey: 8
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Worldwide total number of subjects |
63
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EEA total number of subjects |
35
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
14
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Adolescents (12-17 years) |
49
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at 23 study centers between 15 February 2013 (first subject first visit) and 16 November 2018 (last subject last visit). | ||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
It is a 3 part study (Part 1: Pharmacokinetic assessment, Part 2: (Part 2a-calcium carbonate and lanthanum carbonate [crossover comparison] + Part 2b-lanthanum carbonate], Part 3: lanthanum carbonate treatment for 6 months). | ||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||
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Arms
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Arm title
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Overall Study | ||||||||||||||||||||||||||||
Arm description |
Study was conducted in 3 parts, subjects aged 10 to 12 years received 500 milligram (mg) and greater than (>) 12 years received 1000 milligram single dose of lanthanum carbonate oral powder respectively during part 1. Followed by part 2 during when subjects received calcium carbonate tablet for 8 weeks until a maximum daily dose of 6500 mg was reached (part 2a-Treatment period 1) and then received lanthanum carbonate oral powder for 8 weeks at a daily dose of 1500 mg was reached (part 2a-Treatment period 2). Eligible subjects received lanthanum carbonate oral powder for 8 weeks at a daily dose of 1500 mg, which was titrated bi-weekly until a daily dose of 3000 mg was achieved (part 2b). Subjects who completed part 2 continued the same treatment for additional 6 months during the part 3. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Lanthanum carbonate
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Investigational medicinal product code |
SPD405
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Other name |
Fosrenol
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Pharmaceutical forms |
Powder for oral solution in sachet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects aged 10 to 12 years received 500 mg and >12 years received 1000 milligram single dose of lanthanum carbonate oral powder during Part 1 and at a daily dose of 1500 mg in part 2 and 3000 mg in part 3.
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Investigational medicinal product name |
Calcium carbonate
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received calcium carbonate until the target serum phosphorus level achieved or until a maximum daily dose of 6500 mg was reached, once the serum phosphorus control was achieved the dose was maintained until the end of 8 week treatment period (Part 2a: treatment period 1).
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| Notes [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Milestone is added here to provide more clarity about the subject movement within the study. |
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
Study was conducted in 3 parts, subjects aged 10 to 12 years received 500 milligram (mg) and greater than (>) 12 years received 1000 milligram single dose of lanthanum carbonate oral powder respectively during part 1. Followed by part 2 during when subjects received calcium carbonate tablet for 8 weeks until a maximum daily dose of 6500 mg was reached (part 2a-Treatment period 1) and then received lanthanum carbonate oral powder for 8 weeks at a daily dose of 1500 mg was reached (part 2a-Treatment period 2). Eligible subjects received lanthanum carbonate oral powder for 8 weeks at a daily dose of 1500 mg, which was titrated bi-weekly until a daily dose of 3000 mg was achieved (part 2b). Subjects who completed part 2 continued the same treatment for additional 6 months during the part 3. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
Study was conducted in 3 parts, subjects aged 10 to 12 years received 500 milligram (mg) and greater than (>) 12 years received 1000 milligram single dose of lanthanum carbonate oral powder respectively during part 1. Followed by part 2 during when subjects received calcium carbonate tablet for 8 weeks until a maximum daily dose of 6500 mg was reached (part 2a-Treatment period 1) and then received lanthanum carbonate oral powder for 8 weeks at a daily dose of 1500 mg was reached (part 2a-Treatment period 2). Eligible subjects received lanthanum carbonate oral powder for 8 weeks at a daily dose of 1500 mg, which was titrated bi-weekly until a daily dose of 3000 mg was achieved (part 2b). Subjects who completed part 2 continued the same treatment for additional 6 months during the part 3. | ||
Subject analysis set title |
Part 1: Lanthanum Carbonate
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects aged 10 to 12 years received 500 mg and greater than (>) 12 years received 1000 mg single dose of lanthanum carbonate oral powder.
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Subject analysis set title |
Part 2: Calcium Carbonate
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects received calcium carbonate oral tablet until the target serum phosphorus level achieved or until a maximum daily dose of 6500 mg was reached and once serum phosphorus control was achieved the dose was maintained until the end of 8 weeks (Part 2a: treatment period 1)
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Subject analysis set title |
Part 2: Lanthanum Carbonate
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects received lanthanum carbonate powder orally at a daily dose of 1500 mg mixed into meals and given three times a day or twice daily with a single dose not exceeding 1000 mg, once the serum phosphorus control was achieved the dose was maintained until the end of 8 week (Part 2a: treatment period 2), also subjects received lanthanum carbonate powder orally at a daily dose of 1500 mg mixed into meals and given three times a day or twice daily with a single dose not exceeding 1000 mg, total daily dose was titrated bi-weekly until a maximum dose of 3000 mg was reached and once the serum phosphorus control was achieved the dose was maintained until the end of 8 week (Part 2b).
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Subject analysis set title |
Part 2 + Part 3: Lanthanum Carbonate
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects received lanthanum carbonate powder at a daily dose of 1500 mg mixed into meals and given three times a day or twice daily with a single dose not exceeding 1000 mg, total daily dose was titrated bi-weekly until a maximum dose of 3000 mg was reached and once the serum phosphorus control was achieved the dose was maintained until the end of 8 week treatment period (Part 2a and Part 2b) and continue to receive lanthanum carbonate for additional 6 months (Part 3).
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End point title |
Percentage of Subjects Achieving Age-Specific Kidney Disease Outcomes Quality Initiative (KDOQI) Targets for Serum Phosphate Level Following 8 Weeks of Lanthanum Carbonate Administration (Part 2 + Part 3) [1] | ||||||||
End point description |
KDOQI serum phosphorus targets were defined for: Adolescents aged greater than or equal to (>=) 12 to less than (<) 18 years to be less than or equal to (<=) 5.5 milligrams per deciliter (mg/dL) (1.78 millimoles per liter [mmol/L]); Children aged >=10 years to <12 years to be <= 6.0 mg/dL (1.94 mmol/L). Percentage of subjects achieving age-specific KDOQI targets for serum phosphate level was reported only for the subjects who have received lanthanum carbonate during part 2 or part 3. Per-protocol set 2 (PP2) included subjects who had taken at least 1 dose of investigational product and complete 8 weeks of treatment with lanthanum carbonate and who have serum phosphate assessment data available during Part 2 or Part 3 to
allow summarizing the percentage of subjects achieving age-specific KDOQI target.
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End point type |
Primary
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End point timeframe |
After 8 weeks of lanthanum carbonate administration
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis was not performed for this single arm analysis. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects Achieving Age-Specific Kidney Disease Outcomes Quality Initiative (KDOQI) Targets for Serum Phosphate Level During Part 2 | ||||||||||||
End point description |
KDOQI serum phosphorus targets was defined for: Adolescents aged >= 12 < 18 years to be <= 5.5 mg/dL (1.78 [mmol/L]); Children aged >=10 years to <12 years to be <= 6.0 mg/dL (1.94 mmol/L). Percentage of subjects achieving age-specific KDOQI targets for serum phosphate level were reported only for the subjects who have received calcium carbonate followed by 8 weeks of treatment with lanthanum carbonate in Part 2.Per Protocol Set 1 (PP1) included subjects who had taken at least 1 dose of investigational product and complete 8 weeks of calcium carbonate followed by 8 weeks of lanthanum carbonate and who have serum phosphate assessment data available during Part 2 to allow summarizing the percentage of subjects achieving age-specific KDOQI target.
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End point type |
Secondary
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End point timeframe |
Up to 19 weeks
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Serum Phosphorus Levels Following Treatment With Lanthanum Carbonate After 8 Weeks | ||||||||
End point description |
Changes from baseline in serum phosphorus levels in hyperphosphatemic children and adolescents with chronic kidney disease (CKD) who are on dialysis, following treatment with lanthanum carbonate for 8 weeks were combined and reported baseline was defined as the last assessment prior to the first dose of investigational product. PP2 included subjects who had taken at least 1 dose of investigational product and complete 8 weeks of treatment with lanthanum carbonate and who have serum phosphate assessment data available during Part 2 or Part 3 to allow summarizing the percentage of subjects achieving age-specific KDOQI target.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 8
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Calcium Levels Following Treatment With Lanthanum Carbonate After Week 8 | ||||||||
End point description |
Changes from baseline in calcium levels in hyperphosphatemic children and adolescents with CKD who are on dialysis, following treatment with lanthanum carbonate for 8 weeks were reported were combined and reported baseline was defined as the last assessment prior to the first dose of investigational product. PP2 included subjects who had taken at least 1 dose of investigational product and complete 8 weeks of treatment with lanthanum carbonate and who have serum phosphate assessment data available during Part 2 or Part 3 to allow summarizing the percentage of subjects achieving age-specific KDOQI target.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 8
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Calcium-Phosphorus Product Levels Following Treatment With Lanthanum Carbonate After Week 8 | ||||||||
End point description |
Changes from baseline in calcium-phosphorus product levels in hyperphosphatemic children and adolescents with CKD who are on dialysis, following treatment with lanthanum carbonate for 8 weeks were reported were combined and reported baseline was defined as the last assessment prior to the first dose of investigational product. PP2 included subjects who had taken at least 1 dose of investigational product and complete 8 weeks of treatment with lanthanum carbonate and who have serum phosphate assessment data available during
Part 2 or Part 3 to allow summarizing the percentage of subjects achieving age-specific KDOQI target.
millimole square per square liter (mmol^2/L^2)
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End point type |
Secondary
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End point timeframe |
Baseline, Week 8
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Serum Phosphorus Levels Following Treatment With Calcium Carbonate After 8 Weeks and Lanthanum Carbonate After 8 Weeks During Part 2 | ||||||||||||
End point description |
Changes from baseline in serum phosphorus levels in hyperphosphatemic children and adolescents with CKD who are on dialysis, following treatment with calcium carbonate after 8 weeks and lanthanum carbonate after 8 weeks were combined and reported. Baseline was defined as the last assessment prior to the first dose of investigational product. PP1 included subjects who had taken at least 1 dose of investigational product and complete 8 weeks of calcium carbonate followed by 8 weeks of lanthanum carbonate and who have serum
phosphate assessment data available during Part 2 to allow summarizing the percentage of subjects achieving age-specific KDOQI target.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 8
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Calcium Levels Following Treatment With Calcium Carbonate After 8 Weeks and Lanthanum Carbonate After 8 Weeks During Part 2 | ||||||||||||
End point description |
Changes from baseline in calcium levels in hyperphosphatemic children and adolescents with CKD who are on dialysis, following treatment with calcium carbonate after 8 weeks and lanthanum carbonate after 8 weeks were combined and reported. Baseline was defined as the last assessment prior to the first dose of investigational product. PP1 included subjects who had taken at least 1 dose of investigational product and complete 8 weeks of calcium carbonate followed by 8 weeks of lanthanum carbonate and who have serum phosphate assessment data available during Part 2 to allow summarizing the percentage of subjects achieving age-specific KDOQI target.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 8
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Calcium-Phosphorus Product Levels Following Treatment With Calcium Carbonate After 8 Weeks and Lanthanum Carbonate After 8 Weeks During Part 2 | ||||||||||||
End point description |
Changes from baseline in calcium-phosphorus product levels in hyperphosphatemic children and adolescents with CKD who are on dialysis, following treatment with calcium carbonate after 8 weeks and lanthanum carbonate after 8 weeks were combined and reported. Baseline was defined as the last assessment prior to the first dose of investigational product. PP1 included subjects who had taken at least 1 dose of investigational product and complete 8 weeks of calcium carbonate followed by 8 weeks of lanthanum carbonate and who have serum phosphate assessment data available during Part 2 to allow summarizing the percentage of subjects achieving age-specific KDOQI target.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 8
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Serum Phosphorus Levels at the Last Visit of 8-Week Treatment Period in Part 2 and Monthly During 6-Month Extension Phase of Part 3 | ||||||||||||||||||||||
End point description |
Change from baseline in serum phosphorus levels at the last visit of each 8-week treatment period during Part 2 and monthly during the 6-month extension phase (Part 3) were reported. Baseline was defined as the last assessment prior to the first dose of investigational product. PP2 included subjects who had taken at least 1 dose of investigational product and complete 8 weeks of treatment with lanthanum carbonate and who have serum phosphate assessment data available during Part 2 or Part 3 to allow summarizing the percentage of subjects achieving age-specific KDOQI target. Here, n = number of subjects evaluable at the specific category time points.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 8, 12, 16, 20, 24, 28 and Week 32
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| No statistical analyses for this end point | |||||||||||||||||||||||
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End point title |
Change From Baseline in Calcium Levels at the Last Visit of 8-Week Treatment Period in Part 2 and Monthly During 6-Month Extension Phase of Part 3 | ||||||||||||||||||||||
End point description |
Change from baseline in calcium levels at the last visit of each 8-week treatment period during Part 2 and monthly during the 6- month extension phase (Part 3) were reported.Baseline was defined as the last assessment prior to the first dose of investigational product. PP2 included subjects who had taken at least 1 dose of investigational product and complete 8 weeks of treatment with lanthanum carbonate and who have serum phosphate assessment data available during Part 2 or Part 3 to allow summarizing the percentage of
subjects achieving age-specific KDOQI target. Here, n = number of subjects evaluable at the specific category time points.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 8, 12, 16, 20, 24, 28 and Week 32
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| No statistical analyses for this end point | |||||||||||||||||||||||
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End point title |
Change From Baseline in Calcium-Phosphorus Product Levels at the Last Visit of 8-Week Treatment Period in Part 2 and Monthly During 6-Month Extension Phase of Part 3 | ||||||||||||||||||||||
End point description |
Change from baseline in calcium-phosphorus product levels at the last visit of each 8-week treatment period during Part 2 and monthly during the 6-month extension phase (Part 3) were reported.Baseline was defined as the last assessment prior to the first dose of investigational product.PP2 included subjects who had taken at least 1 dose of investigational product and complete 8 weeks of treatment with lanthanum carbonate and
who have serum phosphate assessment data available during Part 2 or Part 3 to allow summarizing the percentage of subjects achieving age-specific KDOQI target. Here, n = number of subjects evaluable at the specific category time points.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 8, 12, 16, 20, 24, 28 and Week 32
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| No statistical analyses for this end point | |||||||||||||||||||||||
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End point title |
Change From Baseline in Biochemical Bone Markers | |||||||||||||||||||||||||||||||||||||||
End point description |
Change from baseline in bone turnover markers including bone alkaline phosphatase (ALP), osteocalcin, and sclerostin was reported for combined Part 2 and 3. PP1 included subjects who had taken at least 1 dose of investigational product and complete 8 weeks of calcium carbonate followed by 8 weeks of lanthanum carbonate and who have serum phosphate assessment data available during Part 2 to allow summarizing the percentage of subjects achieving age-specific KDOQI target. End of study is the completion if the subjects has
benefited from and desires to continue dosing with lanthanum. Here,'99999' in the reported data indicate that the respective subject analysis set was not applicable to the category and n = number of subjects evaluable for each subject analysis set at the specific category time points.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 8, Week 16 and EOS
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||
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End point title |
Change From Baseline in Biochemical Bone Markers for Tartrate-Resistant Acid Phosphatase (TRAP) | |||||||||||||||||||||
End point description |
Change from baseline in bone turnover markers for, tartrate-resistant acid phosphatase (TRAP) was reported for combined Part 2 and 3. PP1 included subjects who had taken at least 1 dose of investigational product and complete 8 weeks of calcium carbonate followed by 8 weeks of lanthanum carbonate and who have serum phosphate assessment data available during Part 2 to allow summarizing the percentage of subjects achieving age-specific KDOQI target. Here,'99999' in the reported data indicate that the respective subject analysis set was not applicable to the category and n = number of subjects evaluable for each subject analysis set at the specific category time points.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 8, Week 16 and EOS
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Change From Baseline in Biochemical Bone Markers for Fibroblast Growth Factor 23 (FGF-23) | |||||||||||||||||||||
End point description |
Change from baseline in bone turnover markers including fibroblast growth factor 23 (FGF-23) was reported for combined Part 2 and 3. PP1 included subjects who had taken at least 1 dose of investigational product and complete 8 weeks of calcium carbonate followed by 8 weeks of lanthanum carbonate and who have serum phosphate assessment data available during Part 2 to allow summarizing the percentage of subjects achieving age-specific KDOQI target. Here,'99999' in the reported data indicate that the respective subject analysis set was not applicable to the category and n = number of subjects evaluable for each subject analysis set at the specific category time points.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 8, Week 16 and EOS
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Change From Baseline in Biochemical Bone Markers for Parathyroid Hormone (PTH) | |||||||||||||||||||||
End point description |
Change from baseline in bone turnover markers for parathyroid hormone was reported for combined Part 2 and 3. PP1 included subjects who had taken at least 1 dose of investigational product and complete 8 weeks of calcium carbonate followed by 8 weeks of lanthanum carbonate and who have serum phosphate assessment data available during Part 2 to allow summarizing the percentage of subjects achieving age-specific KDOQI target. Here,'99999' in the reported data indicate that the respective subject analysis set was not applicable to the category and n = number of subjects evaluable for each subject analysis set at the specific category time points.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 8, Week 16 and EOS
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Change From Baseline in Biochemical Bone Markers for fetuin-A | |||||||||||||||||||||
End point description |
Change from baseline in bone turnover markers for fetuin-A was reported for combined Part 2 and 3. PP1 included subjects who had taken at least 1 dose of investigational product and complete 8 weeks of calcium carbonate followed by 8 weeks of lanthanum carbonate and who have serum phosphate assessment data available during Part 2 to allow summarizing the percentage of subjects achieving age-specific KDOQI target. Here,'99999' in the reported data indicate that the respective subject analysis set was not applicable to the category and n = number of subjects evaluable for each subject analysis set at the specific category time points.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 8, Week 16 and EOS
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Change From Baseline in Height | |||||||||||||||||||||
End point description |
Change from baseline in height for combined Part 2 and Part 3 for each drug at Week 8, 16 and end of study was reported. PP1 included subjects who had taken at least 1 dose of investigational product and complete 8 weeks of calcium carbonate followed by 8 weeks of lanthanum carbonate and who have serum phosphate assessment data available during Part 2 to allow summarizing the percentage of subjects achieving age-specific KDOQI target. Here,'99999' in the reported data indicate that the respective subject analysis set was not applicable to the category and n = number of subjects evaluable for each subject analysis set at the specific category time points.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 8, Week 16, and EOS
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Change From Baseline in Weight | |||||||||||||||||||||
End point description |
Change from baseline in weight for combined Part 2 and Part 3 for each drug at Week 8, 16 and end of study (EOS) was reported. PP1 included subjects who had taken at least 1 dose of investigational product and complete 8 weeks of calcium carbonate followed by 8 weeks of lanthanum carbonate and who have serum phosphate assessment data available during Part 2 to allow summarizing the percentage of subjects achieving age-specific KDOQI targets. Here,'99999' in the reported data indicate that the respective subject analysis set was not applicable to the category and n = number of subjects evaluable for each subject analysis set at the specific category time points.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 8, Week 16, and EOS
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| No statistical analyses for this end point | ||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From start of study drug administration up to follow-up (up to Week 42)
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.1
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Reporting groups
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Reporting group title |
Part 1: Lanthanum Carbonate
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Reporting group description |
Subjects aged 10 to 12 years received 500 mg and >12 years received 1000 mg single dose of lanthanum carbonate oral powder. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part 2 + Part 3: Lanthanum Carbonate
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Reporting group description |
Subjects received lanthanum carbonate powder at a daily dose of 1500 mg mixed into meals and given three times a day or twice daily with a single dose not exceeding 1000 mg, total daily dose was titrated bi-weekly until a maximum dose of 3000 mg was reached and once the serum phosphorus control was achieved the dose was maintained until the end of 8 week treatment period (Part 2a and Part 2b) and continue to receive lanthanum carbonate for additional 6 months (Part 3). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Part 2: Calcium Carbonate
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Reporting group description |
Subjects received calcium carbonate oral tablet until the target serum phosphorus level achieved or until a maximum daily dose of 6500 mg was reached and once serum phosphorus control was achieved the dose was maintained until the end of 8 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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13 Jul 2012 |
Amendment 1 included the following changes - Addition of sclerostin and fetuin-A parameters to the assay for biochemical bone markers. Correction of error in dosing regimen in Parts 1 and 2. Clarification and correction of washout periods, and assessments required. Addition of guidance language in relation to dosing in case of hypophosphatemia and/or hypocalcemia during Parts 2 and 3 or hypercalcemia while taking calcium carbonate in Part 2. PTH designated as a biochemical bone marker but was to be analyzed as part of the routine biochemistry panel. Biochemistry parameters amended to include vitamin D at baseline and end of study. |
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24 Sep 2012 |
Amendment 2 included the following changes - Addition of confirmatory phosphorus value to washout period visits W1 and W2. Clarification that subjects may start lanthanum carbonate treatment at Visit 2.4 if phosphorus criterion is met. Confirmation that subjects will not be withdrawn from the study if they do not meet phosphorus criteria after Visit 2.4 but will start lanthanum carbonate therapy and be assessed for Part 3. These subjects cannot be included in the per-protocol set. Correction that lanthanum carbonate is taken with meals. Clarification of which secondary endpoints (height or length, head circumference, and weight) are to be measured at subject visits. |
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17 Apr 2014 |
Amendment 3 included the following changes - Age range amended from 6 months to <18 years to 10 years to <18 years. Reduction in Part 3 from 10 months to 6 months and overall exposure to lanthanum reduced from 12 months to 8 months. Change in serious adverse events and pregnancy notification from 1 business day to 24 hours. Extension in safety follow-up period from 7 days after last visit to 7-14 days from the last dose of investigational product, except for subjects who undergo kidney transplant, whose follow-up telephone call will be 30+/-7 days after the last dose of investigational product. Added that calcium levels, in
addition to phosphorus levels, should be measured locally for titration purposes during the first treatment period of Part 2. Removal of exclusion criterion relating to serum calcium level. Starting dose of lanthanum carbonate in the second treatment period of Part 2 amended to reflect the change in age range of subjects. All subjects to be given a 1500 mg starting dose. Clarification that the lanthanum carbonate given in Parts 2 and 3 should be mixed with food and divided equally between all meals. Clarification that titration should continue until serum phosphorus levels meet KDOQI age guidelines. Correction made to age range of subjects with
phosphorus level >6.0 mg/dL. Clarified acceptable dose levels in Part 3. Clarified how the per-protocol set will be determined. Sample size justification added. Study period extended to December 2015. |
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02 Mar 2015 |
Amendment 4 included the following changes - Protocol revised to match updated SAP (Redefined full analysis set, Redefined Safety Analysis Set 3, Described subject disposition for all study parts, Described summarization methods for demographic and baseline characteristics (updated to align with finalized SAP), Described intent for listing and analyzing investigational product exposure, Described methods for listing prior and concomitant medication, Described safety analyses). Updated study duration to 44 months (extended to 2016). |
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18 Oct 2016 |
Amendment 5 included the following changes - Removed the active comparator (calcium carbonate) treatment arm given the extreme difficulty in recruiting enough subjects to obtain the originally proposed sample size of at least 50 subjects required for the per-protocol set for a crossover non-inferiority study. The original design of Part 2 of Study SPD405-207 was crossover non-inferiority to allow a formal comparison of the efficacy of lanthanum carbonate with calcium carbonate (Part 2a). Under the modified study design, Part 2a has been removed and subjects will only be treated with 8 weeks of lanthanum carbonate in Part 2b of the study for short-term efficacy and safety assessment. Adjusted planned sample size from 72 to 65, with the target to enroll at least 35 subjects (instead of at least 50) who complete 8 weeks of treatment with lanthanum carbonate and are assessable for the primary endpoint, due to low replenishment of eligible subjects and the discontinuation of subjects enrolled in the study, in
agreement with Paediatric Committee of the European Medicine Agency. Added that Part 1, single dose, pharmacokinetic assessment of lanthanum carbonate, is complete and the interim clinical study report interpreting and summarizing the data is available. Added or modified the primary and secondary objectives. As a result of the change in the study design, it is no longer necessary to replace subjects who discontinue Part 2 to ensure that 35 subjects enter Part 3 of the study. Updated study duration to 64 months (extended to 2018). Modified or redefined analysis populations. Clarified that the full analysis set and PP2 will be used for the primary endpoint analyses, while the FAS, PP1, and PP2 will be used for the secondary efficacy endpoint analyses. Updated primary and secondary variables to align with the changes made to the primary and secondary objectives and to the definition of analysis populations. Adjusted the planned sample size. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
